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Cancer research is striving toward new frontiers of assigning the correct personalized drug(s) to a given patient. However, extensive tumor heterogeneity poses a major obstacle. Tumors of the same type often respond differently to therapy, due to patient-specific molecular aberrations and/or untargeted tumor subpopulations. It is frequently not possible to determine a priori which patients will respond to a certain therapy or how an efficient patient-specific combined therapy should be designed. Large-scale datasets have been growing at an accelerated pace and various technologies and analytical tools for single cell and bulk level analyses are being developed to extract significant individualized signals from such heterogeneous data. However, personalized therapies that dramatically alter the course of the disease remain scarce, and most tumors still respond poorly to medical care. In this review, the basic concepts of bulk and single cell approaches are discussed, as well as their emerging role in individualized designs of drug therapies, including the advantages and limitations of their applications in personalized medicine. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The precise control of monomer sequence and stereochemistry in copolymerization is of much interest and importance for the synthesis of functional polymers, but studies toward this goal have met with only limited success to date. selleckchem Now, the co-syndiospecific alternating copolymerization of methoxyphenyl- and N,N-dimethylaminophenyl-functionalized propylenes with styrene by half-sandwich rare-earth catalysts is reported. This reaction efficiently afforded the corresponding functionalized propylene-alt-styrene copolymers with a perfect alternating sequence and excellent co-syndiotacticity (rrrr >99 %), thus constituting the first example of co-stereospecific alternating copolymerization of polar and non-polar olefins. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.INTRODUCTION Crohn's Disease (CD) results from chronic inflammation of the gastrointestinal (GI) tract involving TNF-α release. Gastrointestinal electrical stimulation (GES), a form of neuromodulation used to treat upper GI motility symptoms (UGI Sx), exerts an anti-inflammatory effect via TNF-α suppression. We hypothesized patients with CD symptoms in patients with gastroparesis (GP) may respond to GES. METHODS We retrospectively examined 284 patients with symptomatic gastroparesis (Gp Sx), who underwent GES placement. Patients with Gp Sx were evaluated by validated GI Sx patient reported outcome. Scores were obtained at baseline, after temporary GES placement and after permanent GES placement. Eleven patients from this cohort with coexisting CD were analyzed for improvements in their CD symptomatology using the Harvey Bradshaw Index (HBI). link2 HBI scores were compared from before GES to after two sequential applications of electrical stimulation (temporary then permanent). A 3-point decrease in HBI indicated a clinical response and an HBI less then 5 indicated clinical remission after GES. An unadjusted repeated measures model was used in the analysis with statistical significance set at p ≤ 0.05. RESULTS Our cohort prevalence of CD was 3.9% (2 M & 9 F, mean age 49.8 yrs.). Within both the Gp + CD & Gp subgroups, UGI Sx substantially improved after temporary and permanent GES. Furthermore, 55% of the GP + CD subgroup demonstrated a clinical response by HBI, while one patient achieved clinical remission (p  less then  0.01). CD medications were reviewed before and after GES placement, and any interval changes are unlikely to explain the improved HBI scores. DISCUSSION We conclude that both UGI and CD symptoms in GP + CD patients responded well to GES. The interaction of Gp and CD and the effects of neuromodulation on CD symptoms warrant additional investigation. © 2020 International Neuromodulation Society.AIM To assess the effects of dapagliflozin plus saxagliptin plus metformin versus glimepiride plus metformin on liver fat (proton density fat fraction) and visceral and subcutaneous adipose tissue volumes over 52 weeks of treatment. MATERIALS AND METHODS This was a magnetic resonance imaging substudy of a 52-week, multicentre, randomized, double-blind, parallel-group trial that evaluated the efficacy and safety of dapagliflozin 10 mg/day plus saxagliptin 5 mg/day versus titrated glimepiride 1-6 mg (1, 2, 3, 4 or 6 mg) in 82 patients with type 2 diabetes (HbA1c 7.5%-10.5%) on metformin ≥1500 mg/day background. Analyses were exploratory and not controlled for multiplicity; P-values are nominal. RESULTS Magnetic resonance imaging was performed on 59 patients; liver fat and adipose tissue volumes were analysed for 59 and 57 patients, respectively. There was a significant >30% reduction from baseline in liver fat (P = 0.007) and >10% reduction in adipose tissue volumes (P less then  0.01) with dapagliflozin plus saxagliptin plus metformin at week 52 versus glimepiride plus metformin. In the full-study population, dapagliflozin plus saxagliptin plus metformin decreased body weight and serum alanine aminotransferase and aspartate aminotransferase levels over 52 weeks. CONCLUSIONS Dapagliflozin plus saxagliptin significantly decreased liver fat and adipose tissue volume versus glimepiride, and reduced serum liver enzyme levels, indicating a favourable metabolic profile of dapagliflozin plus saxagliptin in patients with type 2 diabetes on metformin therapy. © 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.Herein, we developed a Ru(II)(BPGA) complex that could be used to catalyze chemo- and site-selective C-H oxidation. The described ruthenium complex was designed by replacing one pyridyl group on tris(2-pyridylmethyl)amine with an electron-donating amide ligand that was critical for promoting this type of reaction. More importantly, higher reactivities and better chemo-, and site-selectivities were observed for reactions using the cis-ruthenium complex rather than the trans-one. This reaction could be used to convert sterically less hindered methyne and/or methylene C-H bonds of a various organic substrates, including natural products, into valuable alcohol or ketone products. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.INTRODUCTION This mixed methods study evaluates the use and perceptions of a novel video genre of authentic, in-the-moment expert-student dialogue to support student preparation for a summative clinical competence assessment. METHODS Expert-student dialogue videos were available on the university learning management system (Moodle) for self-directed access for a fixed prosthodontics course. These comprised 3 categories of video relating to dialogic episodes of previous student's performance relating to a clinical competence assessment. These were as follows case suitability, case discussion and self-evaluation. Fourteen students who were taking the competence test and had watched the supporting videos were invited for focus group interviews. Twelve students participated in three focus groups within 24 hours of the assessment and the audio recordings were analysed. A thematic analysis was performed using an inductive approach. Video access data were also retrieved and analysed based on when the videos were watched. RESULTS Three key themes were identified assessment preparation, enhanced learning and affordance phenomena. By accessing the videos, students gained insights into the case suitability, assessment process and criteria, and the examiners' expectations. They reported reduced uncertainty and stress, improved confidence and better preparedness for the assessment. Students also reported this video genre stimulated higher-order thinking and provided a broader clinical experience. A diverse array of viewing patterns was observed immediately before the assessment and across the year. For the focus group of students, they watched 65% of all their videos for the prosthodontics course one week before their competency testing periods. CONCLUSION The expert-student dialogue videos that captured peers clinical competence tests improved students' assessment literacy, increased their assessment preparedness, reduced stress and enriched their learning. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.BACKGROUND As part of a larger study exploring the transition to retirement for people with intellectual disability from a working life in mainstream employment, this paper reports on retirement from the perspective of those who have already retired. METHOD Semi-structured interviews were undertaken with five Australian retirees with intellectual disability. Data were analysed using grounded theory methodology. Employment service records provided background information on participants' employment and supports. RESULTS Retirement occurred as the solution to ongoing problems primarily related to health. Retirement decisions were made in conjunction with family and support staff, with participants reporting varying levels of self-determination in the process, and mixed feelings about their retirement. None of the participants were participating in mainstream community groups in retirement. CONCLUSIONS There is a need for retirement preparation for this emerging population to support self-determination in retirement-related decisions including individualized training to facilitate independent participation in mainstream social activities in retirement. link3 © 2020 John Wiley & Sons Ltd.BACKGROUND Image-guided percutaneous core needle biopsy (PCNB) is increasingly utilized to diagnose solid tumors. The objective of this study is to determine whether PCNB is adequate for modern biologic characterization of neuroblastoma. PROCEDURE A multi-institutional retrospective study was performed by the Pediatric Surgical Oncology Research Collaborative on children with neuroblastoma at 12 institutions over a 3-year period. Data collected included demographics, clinical details, biopsy technique, complications, and adequacy of biopsies for cytogenetic markers utilized by the Children's Oncology Group for risk stratification. RESULTS A total of 243 children were identified with a diagnosis of neuroblastoma 79 (32.5%) tumor excision at diagnosis, 94 (38.7%) open incisional biopsy (IB), and 70 (28.8%) PCNB. Compared to IB, there was no significant difference in ability to accurately obtain a primary diagnosis by PCNB (95.7% vs 98.9%, P = .314) or determine MYCN copy number (92.4% vs 97.8%, P = .111). The yield for loss of heterozygosity and tumor ploidy was lower with PCNB versus IB (56.1% vs 90.9%, P  less then  .05; and 58.0% vs. 88.5%, P  less then  .05). Complications did not differ between groups (2.9 % vs 3.3%, P = 1.000), though the PCNB group had fewer blood transfusions and lower opioid usage. Efficacy of PCNB was improved for loss of heterozygosity when a pediatric pathologist evaluated the fresh specimen for adequacy. CONCLUSIONS PCNB is a less invasive alternative to open biopsy for primary diagnosis and MYCN oncogene status in patients with neuroblastoma. Our data suggest that PCNB could be optimized for complete genetic analysis by standardized protocols and real-time pathology assessment of specimen quality. © 2020 Wiley Periodicals, Inc.